Large cell carcinoma of the lung pathophysiology: Difference between revisions

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==Overview==
==Overview==
Large cell carcinoma of the lung arises from the epithelial cells of the lung, which are usually involved in the lining of the airways. The pathological irritation causes the mucus-secreting ciliated [[Pseudostratified epithelium|pseudostratified columnar respiratory epithelial cells]] to be replaced by [[stratified squamous epithelium]]. Large cell carcinoma of the lung has a peripheral location, and usually appears as a well-circumcised mass attached to the [[thoracic wall]]. Large cell carcinoma of the lung is a rapidly growing cancer. The histologic subtype of large cell neuroendocrine tumor is related with a more aggressive presentation. Genes involved in the pathogenesis of large cell carcinoma of the lung, include: [[EGFR]], LKB1, [[KRAS]], HER2, and ALK. On gross pathology, large cell carcinoma of the lung is characterized by well-defined borders, spherical morphology, homogeneous gray-white surface, and bulging appearance. On micropathology, large cell carcinoma of the lung is characterized by the larger size of the anaplastic cells, a higher cytoplasmic-to-nuclear size ratio, and a lack of "salt-and-pepper" chromatin. On immunohistochemistry characteristic features of large cell carcinoma of the lung, include: loss of staining with CK5/6, and positive immunoreactivity to EGFR, PDGFR-alpha, and c-kit.<ref name="pmid24163740">{{cite journal |vauthors=Davidson MR, Gazdar AF, Clarke BE |title=The pivotal role of pathology in the management of lung cancer |journal=J Thorac Dis |volume=5 Suppl 5 |issue= |pages=S463–78 |year=2013 |pmid=24163740 |pmc=3804871 |doi=10.3978/j.issn.2072-1439.2013.08.43 |url=}}</ref>
Large cell carcinoma of the lung arises from the epithelial cells of the lung, which are usually involved in the lining of the airways. The pathological irritation causes the mucus-secreting ciliated [[Pseudostratified epithelium|pseudostratified columnar respiratory epithelial cells]] to be replaced by [[stratified squamous epithelium]]. Large cell carcinoma of the lung has a peripheral location, and usually appears as a well-circumcised mass attached to the [[thoracic wall]]. Large cell carcinoma of the lung is a rapidly growing cancer. The histologic subtype of large cell neuroendocrine tumor is related with a more aggressive presentation. Genes involved in the [[pathogenesis]] of large cell carcinoma of the lung, include: [[EGFR]], LKB1, [[KRAS]], [[HER2]], and ALK. On gross pathology, large cell carcinoma of the lung is characterized by well-defined borders, spherical morphology, homogeneous gray-white surface, and bulging appearance. On micropathology, large cell carcinoma of the lung is characterized by the larger size of the anaplastic cells, a higher cytoplasmic-to-nuclear size ratio, and a lack of "salt-and-pepper" [[chromatin]]. On immunohistochemistry characteristic features of large cell carcinoma of the lung, include: loss of staining with CK5/6, and positive immunoreactivity to [[EGFR]], [[PDGFR]]-alpha, and c-kit.


==Pathogenesis==
==Pathogenesis==
*Large cell carcinoma of the lung arises from the epithelial cells of the lung, which are usually involved in the lining of the airways
*Large cell carcinoma of the lung arises from the [[epithelial cells]] of the [[lung]], which are usually involved in the lining of the [[airways]].
*The pathological irritation causes the mucus-secreting ciliated pseudostratified columnar respiratory epithelial cells to be replaced by stratified squamous epithelium.
*The pathological irritation causes the [[mucus]]-secreting ciliated [[Pseudostratified epithelium|pseudostratified]] [[Columnar epithelia|columnar]] respiratory epithelial cells to be replaced by [[stratified squamous epithelium]].<ref name="pmid24163740">{{cite journal |vauthors=Davidson MR, Gazdar AF, Clarke BE |title=The pivotal role of pathology in the management of lung cancer |journal=J Thorac Dis |volume=5 Suppl 5 |issue= |pages=S463–78 |year=2013 |pmid=24163740 |pmc=3804871 |doi=10.3978/j.issn.2072-1439.2013.08.43 |url=}}</ref>
*Large cell carcinoma of the lung has a peripheral location, and usually appears as a well-circumcised mass attached to the thoracic wall
*Large cell carcinoma of the lung has a peripheral location, and usually appears as a well-circumcised mass attached to the thoracic wall.
*Large cell carcinoma of the lung is a rapidly growing cancer
*Large cell carcinoma of the lung is a rapidly growing cancer.
*The histologic subtype of large cell neuroendocrine tumor is related with a more aggressive presentation<ref name="pmid24163740" />
*The histologic subtype of large cell [[Neuroendocrine tumors|neuroendocrine tumor]] is related with a more aggressive presentation.<ref name="pmid24163740" />


=== Precursor lesions ===
=== Precursor lesions ===
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!Precursor lesions
!Precursor lesions
|-
|-
|Adjacent squamous dysplasia
|Adjacent squamous [[dysplasia]]
|
|Bronchial preneoplastic lesions
* Adjacent squamous dysplasia
 
* Bronchial preneoplastic lesions
|-
|-
|Lymphoepithelioma-like carcinoma
|Lymphoepithelioma-like carcinoma
|
|[[EBV|EBV viral infection]] (viral [EBER1] dependent transformation)
* EBV viral infection (viral (EBER1) dependent transformation)
|}
|}


=== Histogenesis ===
=== Histogenesis ===
* Large cell carcinomas (LCC) commonly originate from a pluripotent progenitor cells.  
* Large cell carcinomas (LCC) commonly originate from a [[Pluripotency|pluripotent]] [[progenitor cells]].  
* The tumour subtypes of LCC generally follows a proximal‐to‐distal distribution pattern moving distally from the trachea.  
* The [[tumor]] subtypes of LCC generally follows a proximal‐to‐distal distribution pattern moving distally from the [[trachea]].  
* Lung tumours initiated by oncogenic K‐Ras activation appeared to be derived from cells located in the bronchioalveolar duct junction (BADJ).  
* Lung tumors initiated by oncogenic [[KRAS|K‐Ras activation]] appeared to be derived from cells located in the bronchioalveolar duct junction (BADJ).  
==== Role of BASCs in large cell carcinoma ====
==== Role of BASCs in large cell carcinoma ====
* Bronchioalveolar duct junction (BADJ) contains cells that expresses both Clara‐specific and alveolar‐specific markers.  
* Bronchioalveolar duct junction (BADJ) contains cells that expresses both Clara‐specific and alveolar‐specific markers.  
* These cells are bronchioalveolar stem cells (BASCs).  
* These cells are bronchioalveolar stem cells (BASCs).  
* Activation of K‐Ras results in differentiation of BASC's leading to adenoma formation.
* Activation of [[KRAS]] results in differentiation of BASC's leading to adenoma formation.
{{familytree/start}}
{{familytree/start}}
{{familytree | | | | | | | | | | A01 | | | | | | | | A01=BASC<br>Dual positive cells}}
{{familytree | | | | | | | | | | A01 | | | | | | | | A01=BASC<br>Dual positive cells}}
Line 50: Line 46:
|-
|-
|
|
* CD133 (prominin-1)
* [[CD133]] (prominin-1)
* CD44 (membrane-bound glycoprotein)
* [[CD44]] (membrane-bound [[glycoprotein]])
* CD133+ESA+
* [[CD133]]+[[ESA]]+
* CD90
* [[CD90]]
* CD87 (uPAR)
* CD87 (uPAR)
* CD166+CD44+ and CD166+EpCAM+
* CD166+ CD44+ and CD166+EpCAM+
|}
|}


=== Two hypotheses explaining the origin of NE variants of large cell carcinoma ===
=== Two hypotheses explaining the origin of NE variants of large cell carcinoma ===
* Neuroendocrine bodies (NEBs)  are cellular bodies in the epithelial lining of the bronchi.
* Neuroendocrine bodies (NEBs)  are cellular bodies in the epithelial lining of the [[bronchi]].
* Neuroendocrine bodies (NEBs) harbor pulmonary neuroendocrine cells (PNECs).
* Neuroendocrine bodies (NEBs) harbor pulmonary neuroendocrine cells (PNECs).
* PNECs are associated with variant Clara expressing cells (vCEs).
* PNECs are associated with variant clara expressing cells (vCEs).
* Mutation or loss of Rb1 gene function along with Trp53 results in neuroendocrine tumors arising from hyperplasia of PNEC.  
* Mutation or loss of [[Rb|Rb1]] gene function along with Trp53 results in [[neuroendocrine tumors]] arising from hyperplasia of PNEC.  


{{familytree/start}}
{{familytree/start}}
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*Development of large cell carcinoma of the lung is the result of multiple [[genetic mutation]]s<ref name="pmid24163740">{{cite journal |vauthors=Davidson MR, Gazdar AF, Clarke BE |title=The pivotal role of pathology in the management of lung cancer |journal=J Thorac Dis |volume=5 Suppl 5 |issue= |pages=S463–78 |year=2013 |pmid=24163740 |pmc=3804871 |doi=10.3978/j.issn.2072-1439.2013.08.43 |url=}}</ref>
*Development of large cell carcinoma of the lung is the result of multiple [[genetic mutation]]s<ref name="pmid24163740">{{cite journal |vauthors=Davidson MR, Gazdar AF, Clarke BE |title=The pivotal role of pathology in the management of lung cancer |journal=J Thorac Dis |volume=5 Suppl 5 |issue= |pages=S463–78 |year=2013 |pmid=24163740 |pmc=3804871 |doi=10.3978/j.issn.2072-1439.2013.08.43 |url=}}</ref>
*Genetic mutations play an important role in the treatment selection for large cell carcinoma of the lung
*Genetic mutations play an important role in the treatment selection for large cell carcinoma of the lung
*[[Genes]] involved in the pathogenesis of large cell carcinoma of the lung, include:<ref name="pmid24488911">{{cite journal |vauthors=Shi WY, Liu KD, Xu SG, Zhang JT, Yu LL, Xu KQ, Zhang TF |title=Gene expression analysis of lung cancer |journal=Eur Rev Med Pharmacol Sci |volume=18 |issue=2 |pages=217–28 |year=2014 |pmid=24488911 |doi= |url=}}</ref>
*[[Genes]] involved in the pathogenesis of large cell carcinoma of the lung include:<ref name="pmid24488911">{{cite journal |vauthors=Shi WY, Liu KD, Xu SG, Zhang JT, Yu LL, Xu KQ, Zhang TF |title=Gene expression analysis of lung cancer |journal=Eur Rev Med Pharmacol Sci |volume=18 |issue=2 |pages=217–28 |year=2014 |pmid=24488911 |doi= |url=}}</ref>
:*[[EGFR]]
:*[[EGFR]]
:*[[ALK-1|ALK]]  
:*[[ALK-1|ALK]]  
Line 83: Line 79:
==Associated Conditions==
==Associated Conditions==
Common conditions associated with large cell carcinoma of the lung include:<ref name="pmid25114839">{{cite journal |vauthors=Kanaji N, Watanabe N, Kita N, Bandoh S, Tadokoro A, Ishii T, Dobashi H, Matsunaga T |title=Paraneoplastic syndromes associated with lung cancer |journal=World J Clin Oncol |volume=5 |issue=3 |pages=197–223 |year=2014 |pmid=25114839 |pmc=4127595 |doi=10.5306/wjco.v5.i3.197 |url=}}</ref>
Common conditions associated with large cell carcinoma of the lung include:<ref name="pmid25114839">{{cite journal |vauthors=Kanaji N, Watanabe N, Kita N, Bandoh S, Tadokoro A, Ishii T, Dobashi H, Matsunaga T |title=Paraneoplastic syndromes associated with lung cancer |journal=World J Clin Oncol |volume=5 |issue=3 |pages=197–223 |year=2014 |pmid=25114839 |pmc=4127595 |doi=10.5306/wjco.v5.i3.197 |url=}}</ref>
* Paraneoplasic syndromes, such as:
* Paraneoplasic syndromes such as:
** Humoral [[hypercalcemia]] of malignancy
** Humoral [[hypercalcemia]] of [[malignancy]].
** Syndrome of inappropriate antidiuretic hormone production
** [[Syndrome of inappropriate antidiuretic hormone]] production
** [[Cushing’s syndrome]]
** [[Cushing’s syndrome]]
** [[Carcinoid syndrome]]
** [[Carcinoid syndrome]]
Line 95: Line 91:
:*Spherical morphology
:*Spherical morphology
:*Homogeneous gray-white surface
:*Homogeneous gray-white surface
:**'''Sectioning''' reveals a soft, pink-tan tumor with frequent [[necrosis]], occasional [[hemorrhage]] and rarely, [[cavitation]].
:**Sectioning reveals a soft, pink-tan tumor with frequent [[necrosis]], occasional [[hemorrhage]] and rarely, [[cavitation]].
:*Bulging appearance
:*Bulging appearance
:**Basaloid carcinomas characteristically show exophytic bronchial growth
:**Basaloid carcinomas characteristically show exophytic bronchial growth
Line 111: Line 107:
!Variant of LCC
!Variant of LCC
!Microscopic pathology
!Microscopic pathology
!Immunohistochemistry
|-
|-
|Large cell neuroendocrine carcinoma (LCNEC)  
|Large cell neuroendocrine carcinoma (LCNEC)  
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* Organoid nesting
* Organoid nesting
* Trabecular growth
* Trabecular growth
* Rosettes and perilobular palisading patterns
* Rosettes and peri-lobular palisading patterns
* The tumour cells are generally large, with moderate to abundant cytoplasm.
* The tumors cells are generally large, with moderate to abundant [[cytoplasm]]
* Nucleoli are frequent, prominent and their presence facilitates separation from small cell carcinoma.
* Nucleoli are frequent, prominent and their presence facilitates separation from small cell carcinoma
* Mitotic counts are typically 11 or more (average 75) per 2 mm2 of viable tumour.
* Mitotic counts are typically 11 or more (average 75) per 2 mm2 of viable tumors
* Large zones of necrosis are common.
* Large zones of necrosis are common  
|Chromogranin
 
Synaptophysin
 
NCAM (CD56) 
 
Around 50% of LCNEC express TTF-1 but expression of CK 1, 5, 10, 14, 20 (34ßE12) is uncommon.
|-
|-
|Basaloid carcinoma
|Basaloid carcinoma
|
|
* Solid nodular or anastomotic trabecular cells.
* Solid nodular or anastomotic trabecular cells
* Invasive growth pattern
* Invasive growth pattern
* Peripheral palisading
* Peripheral palisading
Line 138: Line 126:
* Moderately hyperchromatic nuclei
* Moderately hyperchromatic nuclei
* Absent or focal nucleoli
* Absent or focal nucleoli
* Scant cytoplasm with no nuclear molding
* Scant [[cytoplasm]] with no nuclear molding
* High mitotic rate  
* [[Mitotic|High mitotic rate]]
* Squamous differentiation is absent.
* Squamous differentiation is absent
* Hyalin or mucoid degeneration in the stroma.
* Hyalin or mucoid degeneration in the stroma  
* Comedo type necrosis  
* [[Necrosis|Comedo type necrosis]]
* Rosettes
* Rosettes
|
* Immunohistochemical stains for neuroendocrine markers are geneally negative.
* Cytokeratin expression is as seen in NSCLC
** Includes CK 1, 5, 10, and 14 (34ßE12), markers.
** Basaloid carcinoma does not express TTF-1.
|-
|-
|Lymphoepithelioma-like carcinoma
|Lymphoepithelioma-like carcinoma
|
|
* Syncytial growth pattern
* Syncytial growth pattern
* Large vesicular nuclei
* Large vesicular [[nuclei]]
* Prominent eosinophilic nucleoli
* Prominent eosinophilic nucleoli
* Heavy lymphocytic infiltration  
* Heavy lymphocytic infiltration  
** Lymphocytes admixed with
** [[Lymphocytes]] admixed with
** Plasma cells
** [[Plasma cells]]
** Histiocytes
** [[Histiocytes]]
** Occasional neutrophils or eosinophils
** Occasional [[neutrophils]] or [[eosinophils]]
* Infiltrating in the form of diffuse sheets
* Infiltrating in the form of diffuse sheets
* Intratumoural amyloid deposition.
* Intratumorsal [[amyloid]] deposition
|EBER-1 RNA +
|-
|-
|Clear cell carcinoma
|Clear cell carcinoma
|
|
* Large polygonal tumors cells with water-clear or foamy cytoplasm.
* Large polygonal tumors cells with water-clear or foamy cytoplasm
* Tumor cells may or may not contain glycogen.
* Tumor cells may or may not contain glycogen
|
|-
|-
|Large cell carcinoma with rhabdoid phenotype
|Large cell carcinoma with rhabdoid phenotype
|
|
* Rhabdoid cells, characterized by
* Eosinophilic cytoplasmic globules  consisting of intermediate filaments, which may be positive for vimentin and cytokeratin
** Eosinophilic cytoplasmic globules  consisting of intermediate filaments, which may be positive for vimentin and cytokeratin.
* Pure large cell carcinomas with a rhabdoid phenotype are very rare
** Pure large cell carcinomas with a rhabdoid phenotype are very rare.
* Small foci of adenocarcinoma {1803}, and positive neuroendocrine markers may be seen  
** Small foci of adenocarcinoma {1803}, and positive neuroendocrine markers may be seen.
* Ultrastruscturally the eosinophilic inclusions are composed of aggregates of large intra cytoplasmic paranuclear intermediate filaments  
** Ultrastruscturally the eosinophilic inclusions are composed of aggregates of large intra cytoplasmic paranuclear intermediate filaments.
* Cells with rhabdoid features may be seen focally in other poorly differentiated NSCLC
** Cells with rhabdoid features may be seen focally in other poorly differentiated NSCLC
|
|-
|-
|Mixed
|Mixed
|
|
* Large cell neuroendocrine carcinoma with components of  
* Large cell neuroendocrine carcinoma with components of  
** Adenocarcinoma
** [[Adenocarcinoma]]
** Squamous cell carcinoma
** [[Squamous cell carcinoma]]
** Giant cell carcinoma
** Giant cell carcinoma
** Spindle cell carcinoma
** Spindle cell carcinoma
* Histologically heterogeneous
* Histologically heterogeneous
|
|}
|}


Line 197: Line 175:
'''<u>Large cell neuroendocrine carcinoma (LCNEC) :</u>'''<br>
'''<u>Large cell neuroendocrine carcinoma (LCNEC) :</u>'''<br>
Positive for atleast one of the following:
Positive for atleast one of the following:
* Chromogranin
* [[Chromogranin]]
* Synaptophysin  
* [[Synaptophysin]]
* NCAM (CD56)   
* NCAM ([[CD56]])   
* Around 50% of LCNEC express TTF-1 but expression of CK 1, 5, 10, 14, 20 (34ßE12) is uncommon.
Around 50% of LCNEC express [[TTF-1]] but expression of CK 1, 5, 10, 14, 20 (34ßE12) is uncommon.
 
'''<u>Basaloid carcinoma:</u>'''
'''<u>Basaloid carcinoma:</u>'''
* Immunohistochemical stains for neuroendocrine markers are geneally negative.  
* Immunohistochemical stains for neuroendocrine markers are geneally negative.  
* Cytokeratin expression is as seen in NSCLC  
* [[Cytokeratin]] expression is as seen in NSCLC  
** Includes CK 1, 5, 10, and 14 (34ßE12), markers.
** Includes CK 1, 5, 10, and 14 (34ßE12) markers
** Basaloid carcinoma does not express TTF-1.
** Basaloid carcinoma does not express TTF-1
'''<u>Lymphoepithelioma-like carcinoma</u>'''<br>EBER-1 RNA +
'''<u>Lymphoepithelioma-like carcinoma</u>'''<br>
 
*EBER-1 RNA +
==Gallery==
<gallery>
Image:Large cell carcinoma of the lung .jpg|'''Micropathology''': Large cell carcinoma of the lung.H&E stain
Image:Large cell carcinoma of the lung.jpg|'''Gross pathology''': Large cell carcinoma of the lung
</gallery>


==References==
==References==

Latest revision as of 21:06, 27 March 2018

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2]

Overview

Large cell carcinoma of the lung arises from the epithelial cells of the lung, which are usually involved in the lining of the airways. The pathological irritation causes the mucus-secreting ciliated pseudostratified columnar respiratory epithelial cells to be replaced by stratified squamous epithelium. Large cell carcinoma of the lung has a peripheral location, and usually appears as a well-circumcised mass attached to the thoracic wall. Large cell carcinoma of the lung is a rapidly growing cancer. The histologic subtype of large cell neuroendocrine tumor is related with a more aggressive presentation. Genes involved in the pathogenesis of large cell carcinoma of the lung, include: EGFR, LKB1, KRAS, HER2, and ALK. On gross pathology, large cell carcinoma of the lung is characterized by well-defined borders, spherical morphology, homogeneous gray-white surface, and bulging appearance. On micropathology, large cell carcinoma of the lung is characterized by the larger size of the anaplastic cells, a higher cytoplasmic-to-nuclear size ratio, and a lack of "salt-and-pepper" chromatin. On immunohistochemistry characteristic features of large cell carcinoma of the lung, include: loss of staining with CK5/6, and positive immunoreactivity to EGFR, PDGFR-alpha, and c-kit.

Pathogenesis

  • Large cell carcinoma of the lung arises from the epithelial cells of the lung, which are usually involved in the lining of the airways.
  • The pathological irritation causes the mucus-secreting ciliated pseudostratified columnar respiratory epithelial cells to be replaced by stratified squamous epithelium.[1]
  • Large cell carcinoma of the lung has a peripheral location, and usually appears as a well-circumcised mass attached to the thoracic wall.
  • Large cell carcinoma of the lung is a rapidly growing cancer.
  • The histologic subtype of large cell neuroendocrine tumor is related with a more aggressive presentation.[1]

Precursor lesions

  • There are no precursor lesions associated with most of the types of large cell carcinoma except for basaloid carcinoma.
Variants of LCC Precursor lesions
Adjacent squamous dysplasia Bronchial preneoplastic lesions
Lymphoepithelioma-like carcinoma EBV viral infection (viral [EBER1] dependent transformation)

Histogenesis

  • Large cell carcinomas (LCC) commonly originate from a pluripotent progenitor cells.
  • The tumor subtypes of LCC generally follows a proximal‐to‐distal distribution pattern moving distally from the trachea.
  • Lung tumors initiated by oncogenic K‐Ras activation appeared to be derived from cells located in the bronchioalveolar duct junction (BADJ).

Role of BASCs in large cell carcinoma

  • Bronchioalveolar duct junction (BADJ) contains cells that expresses both Clara‐specific and alveolar‐specific markers.
  • These cells are bronchioalveolar stem cells (BASCs).
  • Activation of KRAS results in differentiation of BASC's leading to adenoma formation.
 
 
 
 
 
 
 
 
 
BASC
Dual positive cells
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
K‐Ras activation
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adenoma formation
 
 
 
 
 
 
 
Tumor markers for Lung carcinoma

Two hypotheses explaining the origin of NE variants of large cell carcinoma

  • Neuroendocrine bodies (NEBs) are cellular bodies in the epithelial lining of the bronchi.
  • Neuroendocrine bodies (NEBs) harbor pulmonary neuroendocrine cells (PNECs).
  • PNECs are associated with variant clara expressing cells (vCEs).
  • Mutation or loss of Rb1 gene function along with Trp53 results in neuroendocrine tumors arising from hyperplasia of PNEC.
 
 
 
 
 
 
 
 
Pulmonary neuroendocrine cells(variant Clara expressing cells)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Loss of Rb1 + Trp53 function
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Neuroendocrine hyperplasia
 
 
 
 
 
 
 
 

Genetics

  • Development of large cell carcinoma of the lung is the result of multiple genetic mutations[1]
  • Genetic mutations play an important role in the treatment selection for large cell carcinoma of the lung
  • Genes involved in the pathogenesis of large cell carcinoma of the lung include:[2]

Associated Conditions

Common conditions associated with large cell carcinoma of the lung include:[3]

Gross Pathology

  • On gross pathology, characteristic findings of tumors associated with large cell carcinoma of the lung, include:[4]
  • Well-defined borders
  • Spherical morphology
  • Homogeneous gray-white surface
  • Bulging appearance
    • Basaloid carcinomas characteristically show exophytic bronchial growth
  • Size greater than 4cm
  • Peripheral masses (large cell neuroendocrine carcinomas)
  • Tumor often invades visceral pleura, chest wall, or adjacent structures.

Microscopic Pathology

  • On microscopic pathology, characteristic findings of tumors associated with large cell carcinoma of the lung include:[4]
  • Larger size of the anaplastic cells.
  • A higher cytoplasmic-to-nuclear size ratio.
  • Lack of "salt-and-pepper" chromatin.
Variant of LCC Microscopic pathology
Large cell neuroendocrine carcinoma (LCNEC)
  • Organoid nesting
  • Trabecular growth
  • Rosettes and peri-lobular palisading patterns
  • The tumors cells are generally large, with moderate to abundant cytoplasm
  • Nucleoli are frequent, prominent and their presence facilitates separation from small cell carcinoma
  • Mitotic counts are typically 11 or more (average 75) per 2 mm2 of viable tumors
  • Large zones of necrosis are common
Basaloid carcinoma
  • Solid nodular or anastomotic trabecular cells
  • Invasive growth pattern
  • Peripheral palisading
  • Small, monomorphic, cuboidal fusiform
  • Moderately hyperchromatic nuclei
  • Absent or focal nucleoli
  • Scant cytoplasm with no nuclear molding
  • High mitotic rate
  • Squamous differentiation is absent
  • Hyalin or mucoid degeneration in the stroma
  • Comedo type necrosis
  • Rosettes
Lymphoepithelioma-like carcinoma
Clear cell carcinoma
  • Large polygonal tumors cells with water-clear or foamy cytoplasm
  • Tumor cells may or may not contain glycogen
Large cell carcinoma with rhabdoid phenotype
  • Eosinophilic cytoplasmic globules consisting of intermediate filaments, which may be positive for vimentin and cytokeratin
  • Pure large cell carcinomas with a rhabdoid phenotype are very rare
  • Small foci of adenocarcinoma {1803}, and positive neuroendocrine markers may be seen
  • Ultrastruscturally the eosinophilic inclusions are composed of aggregates of large intra cytoplasmic paranuclear intermediate filaments
  • Cells with rhabdoid features may be seen focally in other poorly differentiated NSCLC
Mixed

Immunohistochemistry

On inmunohistochemistry, findings associated with large cell carcinoma of the lung, include:[4]

  • Loss of staining with CK5/6
  • Positive immunoreactivity to EGFR, PDGFR-alpha, and c-kit

Large cell neuroendocrine carcinoma (LCNEC) :
Positive for atleast one of the following:

Around 50% of LCNEC express TTF-1 but expression of CK 1, 5, 10, 14, 20 (34ßE12) is uncommon.

Basaloid carcinoma:

  • Immunohistochemical stains for neuroendocrine markers are geneally negative.
  • Cytokeratin expression is as seen in NSCLC
    • Includes CK 1, 5, 10, and 14 (34ßE12) markers
    • Basaloid carcinoma does not express TTF-1

Lymphoepithelioma-like carcinoma

  • EBER-1 RNA +

References

  1. ↑ 1.0 1.1 1.2 Davidson MR, Gazdar AF, Clarke BE (2013). "The pivotal role of pathology in the management of lung cancer". J Thorac Dis. 5 Suppl 5: S463–78. doi:10.3978/j.issn.2072-1439.2013.08.43. PMC 3804871. PMID 24163740.
  2. ↑ Shi WY, Liu KD, Xu SG, Zhang JT, Yu LL, Xu KQ, Zhang TF (2014). "Gene expression analysis of lung cancer". Eur Rev Med Pharmacol Sci. 18 (2): 217–28. PMID 24488911.
  3. ↑ Kanaji N, Watanabe N, Kita N, Bandoh S, Tadokoro A, Ishii T, Dobashi H, Matsunaga T (2014). "Paraneoplastic syndromes associated with lung cancer". World J Clin Oncol. 5 (3): 197–223. doi:10.5306/wjco.v5.i3.197. PMC 4127595. PMID 25114839.
  4. ↑ 4.0 4.1 4.2 Miller YE (2005). "Pathogenesis of lung cancer: 100 year report". Am. J. Respir. Cell Mol. Biol. 33 (3): 216–23. doi:10.1165/rcmb.2005-0158OE. PMC 2715312. PMID 16107574.


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